CMTM6 promotes migration, invasion, and EMT by interacting with and stabilizing vimentin in hepatocellular carcinoma cells
| Autor: | Leyang Xiang, Chunshan Liu, Jijie Hu, Dinghua Yang, Kunpeng Du, Baiyao Wang, Xiaoting Huang, Anbang Ren, Yunqiang Tang, Yingying Liang, Gengtai Ye, Yawei Yuan |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Carcinoma Hepatocellular Epithelial-Mesenchymal Transition Proliferation CMTM6 lcsh:Medicine Vimentin Biology Immunofluorescence General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences 0302 clinical medicine Invasion Cell Movement Cell Line Tumor medicine Animals Gene silencing HCC Migration Cell Proliferation Tissue microarray medicine.diagnostic_test Research Liver Neoplasms lcsh:R EMT General Medicine digestive system diseases Gene Expression Regulation Neoplastic Blot Reverse transcription polymerase chain reaction 030104 developmental biology Cell culture 030220 oncology & carcinogenesis biology.protein Cancer research Immunohistochemistry |
| Zdroj: | Journal of Translational Medicine, Vol 19, Iss 1, Pp 1-15 (2021) Journal of Translational Medicine |
| ISSN: | 1479-5876 |
| Popis: | BackgroundCKLF like MARVEL transmembrane domain containing 6 (CMTM6) has been associated with the development in many kinds of cancers. However, the roles of CMTM6 in hepatocellular carcinoma (HCC) are largely unknown. Thus, the present study aimed to investigate the function of CMTM6 in HCC.MethodsWe analysed CMTM6 levels and functions using human HCC cell lines, paired HCC and adjacent non-tumorous tissues, and a tissue microarray. CMTM6 expression was silenced using short hairpin RNAs and its was overexpressed from a lentivirus vector. CMTM6 mRNA and protein levels were determined using quantitative real-time reverse transcription PCR and western blotting, respectively. Proliferation, colony formation, migration, and invasion were assessed using a Cell counting kit-8, colony formation, wound-healing, and Matrigel invasion assays, respectively. Immunohistochemistry was used to score the expression of CMTM6 in tissue samples. The localization and binding partners of CMTM6 were investigated using immunofluorescence and coimmunoprecipitation experiments, respectively. A mouse xenograft model was used for in vivo studies.ResultsCompared with that in adjacent, non-cancerous tissue, Here, CMTM6 levels were increased in HCC tissue samples. Silencing ofCMTM6suppressed the proliferation, migration, and invasion of HCC cells. Conversely,CMTM6overexpression enhanced HCC cell invasion, migration, and proliferation. Mechanistically, CMTM6 physically interacts with and stabilizes vimentin, thus inducing epithelial–mesenchymal transition (EMT), which promotes proliferation, migration and invasion. Importantly, in HCC tissues, CMTM6 expression correlated positively with vimentin levels. Poor prognosis of HCC was associated significantly with higher CMTM6 expression.ConclusionsCMTM6 has an important function in HCC proliferation, migration, and invasion, via its interaction with and stabilization of vimentin. CMTM6 might represent a potential biomarker and therapeutic target to treat HCC. |
| Databáze: | OpenAIRE |
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